tbuckley/cabot-search huggingface dataset:
Abstract 14379: The Association of Triglyceride-Rich Lipoproteins With Cognitive Function: ELSA-Brazil (the Brazilian Longitudinal Study of Adult Health)
Authors: Mohanad Hamandi, Giuliano Generoso, Claudia K Suemoto, Isabela M Bensanor, Krishnaji Kulkarni, Raul Santos, Steven R Jones, Michael J Blaha, Peter P Toth, Paulo A Andrade Lotufo, Marcio S Bittencourt
Journal: Circulation (2022)

Background: Plasma triglyceride levels correspond to the sum of the triglyceride (TG) content in triglyceride-rich lipoproteins (TRL) and their remnants. Experimental studies have shown TRL adverse effects in the brain, but there is limited data about their role in cognitive function. We investigated the cross-sectional association of TG and TRL-cholesterol with domain-specific cognitive tests. Methods: A total of 4,443 participants (51±9 years, 54,2% women) without previous cerebrovascular disease and not on lipid-lowering drugs were evaluated using the delayed word recall test, the category fluency test and the trail making test. TRL were measured by the Vertical Auto Profile (VAP) test, an ultracentrifugation method, and TG by the conventional method. Then, we constructed multiple linear regression models to analyze these associations. Results: The mean TRL level was 32.1±12.2 mg/dl, and the median (IQR) TG was 109 (79-153) mg/dl. There was a negative association between TRL and global cognitive z-score after adjustment for age, sex, ethnicity, education, smoking status, physical activity, alcohol use, depression, systolic blood pressure, diabetes, thyrotropic hormone, LDL, HDL, TG and waist circumference (p=0.009), due to the inverse association with trail making test (p=0.009). We found no association between TG with any cognition tests after adjustment. Conclusion: TRL levels measured by VAP are independently associated with the global cognitive and executive function. TG was not associated with cognitive performance.
Abstract 13610: Imbalance Between GCN5L1 Mediated CypD Acetylation and Sirt3 Deacetylase Promotes Mitochondrial Oxidative Stress, Endothelial Dysfunction and Hypertension
Authors: Sergey Dikalov, Liliya Tkachuk, Mingfang Ao, Daniel Fehrenbach, Michael Sack, Anna Dikalova
Journal: Circulation (2022)

Nearly half of adult population has hypertension which is a main risk factor for cardiovascular disease. Mitochondrial dysfunction contributes to hypertension and targeting mitochondria can potentially improve treatment of hypertension. We found hyperacetylation of mitochondrial Cyclophilin D (CypD) in essential hypertension and proposed that CypD acetylation can promote endothelial dysfunction and hypertension. CypD acetylation is mediated by general control of amino acid synthesis 5 like 1 (GCN5L1) protein which is counteracted by deacetylase Sirt3. We tested potential role GCN5L1 and Sirt3 in endothelial dysfunction and hypertension. Western blot of aortic mitochondria showed an increased GCN5L1 level in hypertensive mice coupled with the reduction of Sirt3 deacetylase resulting in 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. We reported pathogenic role of lipid oxidation products isolevuglandins (isoLGs) and scavenging isoLGs by mitochondria-targeted mito2HOBA reduces mitochondrial acetylation. We tested if mitochondrial isoLGs contributes to acetylase/deacetylase imbalance driving CypD acetylation. Treatment with mito2HOBA improves Sirt3 expression and reduces GCN5L1 level resulting in normalization of GCN5L1/Sirt3 ratio and reduced CypD acetylation. To define the pathophysiological role of GCN5L1 in endothelial cells we tested if GCN5L1 depletion prevents cytokine-induced of mitochondrial oxidative stress. Indeed, treatment of human aortic endothelial cells with AngII+TNFα induces mitochondrial O 2 . -, however, GCN5L1 depletion using siRNA completely abrogated the cytokine-induced mitochondrial oxidative stress. To define the role GNC5L1 in pathogenesis of endothelial dysfunction we developed new tamoxifen-inducible endothelial specific GNC5L1 knockout mice (Ec GNC5L1KO ). Depletion of endothelial GCN5L1 reduces vascular mitochondrial O 2 . -, prevents inactivation of endothelial nitric oxide and preserves endothelial dependent relaxation in angiotensin II-infused Ec GNC5L1KO mice compared with wild-type littermates. These data support the pathogenic role of GNC5L1 in CypD acetylation and endothelial dysfunction and targeting GNC5L1 can be beneficial in cardiovascular disease.
Abstract 14406: CD36 Facilitate Macrophage Phagocytosis Through Mitochondrial ROS During Initiation of Atherosclerosis
Authors: Jue Zhang, Jackie Chang, Mirza Ahmar Beg, Yiqiong Zhao, Yiliang Chen
Journal: Circulation (2022)

Introduction: Macrophage-mediated phagocytosis is essential for tissue homeostasis but abnormal phagocytosis may lead to metabolic defect and chronic inflammation. Macrophage-derived lipid-laden foam cell is a hallmark of the early stages of atherosclerosis. However, phagocytosis efficiency in foam cells is not well explored. We previously showed that oxLDL/CD36 signaling in macrophages promoted mitochondrial reactive oxygen species (mtROS) production, foam cell formation, and facilitated diet-induced atherosclerosis. The aim of this study is to investigate the role of CD36-mediated mtROS production in phagocytosis during the early stages of atherosclerosis. Methods and Results: We conducted flow cytometry-based phagocytosis assays using E. coli bioparticles conjugated with pH-sensitive pHrodo® dyes. Utilizing peritoneal murine macrophages, we showed that pre-treatment of oxLDL, but not native LDL or HDL, stimulated phagocytosis efficiency in a dose- and time-dependent manner. However, CD36 deficiency in macrophages attenuated oxLDL-stimulated phagocytosis by ~50%. Reducing mtROS levels either by MitoTempo, a mtROS scavenger, or using MCAT macrophages, which overexpress human catalase in the mitochondria, also significantly decreased oxLDL-stimulated phagocytosis in vitro. To explore the physiological relevance, we conducted in vivo phagocytosis assay by IV injection of pHrodo bioparticles into ApoE -/- and ApoE -/- /CD36 -/- mice after chow or high fat diet (HFD) for 6 weeks. We found that aortic F4/80 + /TREM + foamy macrophages from ApoE -/- mice on HFD showed 1.5-fold increase in phagocytosis compared with those from ApoE -/- mice on chow diet. CD36 deficiency in ApoE -/- mice blocked the HFD-induced phagocytosis in aortic foamy macrophages. Moreover, we investigated the phagocytosis of apoptotic cells (efferocytosis) by macrophages and showed that mtROS-induction is critical for efficient efferocytosis in vivo. Conclusions: OxLDL stimulates macrophage phagocytosis, which is dependent on CD36. CD36-mediated mtROS production is essential for aortic macrophage phagocytosis and may play a role in foam cell formation during the initiation of atherosclerosis.
Abstract 13947: Heparin-Mediated Release of Hepatocyte Growth Factor at the Acute Phase of STEMI
Authors: Simon Leboube, Ahmad Hayek, Alexandre Paccalet, Bruno PILLOT, Camille Brun, Iyad Abousaleh, Cyril PRIEUR, Bertrand Scheppler, Helene Thibault, Gilles Rioufol, Nathan O Mewton, Gabriel Bidaux, Claire Crola Da Silva, Thomas Bochaton
Journal: Circulation (2022)

Introduction: Hepatocyte Growth Factor (HGF) is a cytokine promoting cell survival via its receptor c-met. Heparin injection is known to induce a massive release of native HGF in blood. Heparin is used at the acute phase of myocardial infarction (MI). However, HGF release at the acute phase of MI and its potential cardioprotective effect is unknown. Hypothesis: We aimed to assess HGF kinetics in a cohort of ST-elevation myocardial infarction (STEMI) and its potential cardioprotective effect. Methods: We prospectively included consecutive STEMI patients admitted in our hospital from 2016 to 2019. All patients underwent coronary angiography with revascularization. Sera were collected at 5 time points (admission, 4 hours (H4), H24, H48 and 1 month after STEMI). Samples were stored at -80°C. HGF levels were assess by ELISA. We used a mouse model of myocardial ischemia reperfusion (ligation of the left anterior descending coronary artery followed by reperfusion) to evaluate HGF effect. Results: We included 230 patients. We observed an intense and early peak of HGF as early as admission, before revascularization (8750 pg/ml, IQR [8021-9492]) followed by a rapid decrease within the first 48h (p&lt;0.0001). We demonstrated that this rapid increase was induced by heparin administration (unfractionated heparin or low molecular weight heparins). To evaluate the effect of HGF on myocardial infarct size we administrated HGF or placebo in mice during myocardial reperfusion. In the HGF group, infarct size was significantly smaller compared to the control group (52.0% of left ventricle vs 58.0%, p=0.002). Conclusions: We demonstrated an intense and early HGF peak at the acute phase of STEMI, induced by heparin. In our preclinical mouse model, HGF had cardioprotective effect after MI. Thus we may suppose that heparin-mediated release of HGF at the acute phase of STEMI have cardioprotective effect that may confer a basal cardioprotection in all patients.
Abstract 14249: COVID-19 and Complete Heart Block in a Vaccinated Adult
Authors: Luke Lawrence, Mark Brahier, Monvadi B Srichai-Parsia, Athanasios Thomaides
Journal: Circulation (2022)

Introduction: Complete heart block (CHB) in association with Covid-19 is uncommon and has been described primarily in the pre-vaccine time period. In the setting of acute Covid-19 infection, decision to treat CHB with permanent pacemaker (PPM) is often uncertain as the CHB may resolve or persist. We present a case of reversible CHB and Covid-19 infection in a vaccinated healthy 28-year-old. Case: A healthy 28-year-old female presented after syncope. She had been vaccinated three times against Covid-19 with Pfizer-BioNTech mRNA vaccine with her third dose four months prior. She had known Covid-19 exposure and developed sore throat three days prior to presenting with syncope. She had no other symptoms. Physical exam was remarkable only for bradycardia. Labs showed positive Covid-19 PCR test and elevated troponin of 0.396 ng/mL. Complete blood counts, metabolic panel, ESR and CRP were normal. Lyme IgM and IgG were negative by Western blot. ECG showed CHB with a rate of 35 beats per minute (Figure 1A). Echocardiogram showed no abnormalities. The patient remained in CHB for 24 hours, at which point PPM was implanted after shared-decision making. Post-PPM ECG showed AV-paced rhythm (Figure 1B). At follow up, PPM interrogation showed that she transitioned to sinus rhythm with right bundle branch block (RBBB) followed by a return to normal sinus rhythm without RBBB 5 days after implantation (Figure 1C). Cardiac MRI two months after PPM implantation showed no abnormalities. Discussion: This was a case of Covid-19 associated myocardial injury with CHB in a fully-vaccinated, healthy adult treated with PPM. Despite vaccination, this patient experienced myocardial and conduction system involvement during acute Covid-19 infection. Myocardial injury along with this ECG progression suggested that there was transient inflammation of the myocardial septum resulting in CHB. It may be reasonable to delay PPM implantation in cases of CHB and Covid-19 infection as the CHB may be transient.
Abstract 13990: Even the Perfect Face Can Break Your Heart: A Case of Variant Takotsubo Cardiomyopathy After Facial Reconstruction Surgery
Authors: Mohammed Haji, Rei Mitsuyama, Anshul Parulkar, Gerry Ovide
Journal: Circulation (2022)

Introduction: Mid and basal akinesia of the left ventricular wall is a rare variant of Takotsubo cardiomyopathy (TTC). This form of cardiomyopathy is commonly associated with severe emotional and physical triggers in post-menopausal women, but not typically in younger patients undergoing minimally invasive surgical interventions. Case Description: A 45-year-old female with prior breast augmentation surgery presented to the emergency room after an elective facial reconstruction procedure, complicated by shock. At the end of the procedure, she received a planned phenylephrine challenge by her surgeon to assess the risk of post-op bleeding, after which she developed persistent hypotension. On arrival, the patient was hypotensive, tachycardic, and requiring oxygen. The patient was started on norepinephrine and vasopressin infusions. Initial labs were notable for a troponin of 4,611. EKG showed sinus arrhythmia and diffuse ST depressions. Transthoracic echocardiogram (TTE) showed a left ventricle with moderately reduced systolic function with akinesia of mid and basal segments with preserved contractility of the apex. Left heart catheterization showed no coronary disease and an elevated left ventricular end diastolic pressure. Right heart catheterization on vasopressors revealed elevated pulmonary pressures and a Fick cardiac output/cardiac index of 4/2.3. Given elevated filling pressures, the patient received diuresis as pressors and oxygen were weaned. Prior to discharge, minimal guideline directed management therapy was started due to low blood pressures and a repeat TTE was unchanged. Discussion: This is a rare case of variant TTC associated with facial reconstruction surgery and exposure to an adrenergic agent, both atypical triggers. One hypothesized mechanism of TTC is linked to a catecholamine surge and therefore, adrenergic agonists, such as phenylephrine, and general anesthetics have been reported as contributing to the risk of developing TTC. This case further creates awareness for this syndrome as a post-procedural complication and cause of shock, despite minimal invasiveness and prior tolerance to similar interventions. Additionally, further research of catecholamine drugs as possible risk factors is needed.
Abstract 13655: Relationship of Health-Related Social Needs, Social Determinants of Health, and Hospital Readmission Following Atrial Fibrillation Ablation
Authors: Eva M Holland, Ryan W Walters, Michael H Kim
Journal: Circulation (2022)

Introduction: Prior data report female sex, race, and impoverished populations by income and insurance status as less likely to receive atrial fibrillation (AF) ablation. Beyond this disparity, the impact of Social Determinants of Health (SocDH) in those that receive AF ablation and clinical outcomes is unknown. Using Health-Related Social Needs (HRSNs) as an indicator of SocDH, we assessed hospital readmissions after AF ablation. Methods: The 2010-2019 Nationwide Readmissions Database was queried for ICD-9/10 procedure and diagnosis codes for hospitalizations in which an adult patient underwent AF ablation and then stratified by presence of HRSNs (housing, socioeconomic status [SES], family, employment, and psychosocial) using Z-codes. Outcomes included all-cause 90-day readmission, and length of stay (LOS) and cost at index hospitalization. Unadjusted and adjusted regression models were estimated controlling for age, sex, and comorbidity burden. Results: An estimated 215,640 hospitalizations included AF ablation, of which 0.3% included a patient with a HRSN where housing and SES insecurity were the two most common HRSNs (43% and 40%, respectively). Hospitalizations including a HRSN tended to include younger patients (63 vs. 67 years), male (70% vs. 61%), a lower income quartile, with less private insurance (10% vs. 30%; all p &lt; .001). HRSNs were associated with a 84% higher unadjusted odds of readmission (p &lt; .001); although, this association was reduced to 15% after adjustment (p = .299). Readmission causes were identical between groups (18% and 15%, respectively). At index hospitalization, after adjustment, HRSNs were associated with 76% longer LOS (p &lt; .001) and 7% higher hospital cost (p = .024). Conclusions: HRSNs/SocDH were associated with significant cost and LOS increases during index AF Ablation hospitalization. All-cause 90-day readmissions were increased, but not significant after adjustment for clinical factors. Compared to the general AF population, those receiving AF ablations had lower prevalence of HRSNs (0.3 vs. 0.9%). Further study on the impact of HRSNs in AF patients regarding rhythm control, AF ablation, and clinical outcomes is needed. A lower prevalence of HRSNs suggests a disparity in AF ablation application.
Abstract 14205: WAVES - The Lucile Packard Children's Hospital Open-Access Pediatric Physiological Waveforms Dataset
Authors: Gurpreet S Dhillon, Daniel R Miller, Nicholas Bambos, Andrew Shin, David Scheinker
Journal: Circulation (2022)

Introduction: Research repositories of adult physiological waveform (PW) data facilitate clinical and methodological advances. Models trained on adult data do not generalize well to pediatric groups. No large, open repository of pediatric PW data is available for research. Methods: PW and vital sign data were downloaded from bedside patient monitoring systems at an academic pediatric hospital from 06/2008-01/2017, de-identified, cleaned, organized, and stored on a research platform managed by Stanford University. Algorithms to process data for deep learning applications were designed, validated, and uploaded to the research platform. Results: WAVES is a single-institution dataset comprising 9 years of high-frequency PW data. WAVES consists of 10.6 million hours of 1 to 20 concurrent types of high-frequency PWs (Table 1). Approximately 1.5 million PW samples were collected over 50,364 unique hospital encounters across various specialized and general units (Table 2). Initial work demonstrated the suitability of the data for training deep learning models by accurately detecting hypotension with data only from electrocardiogram, plethysmography, and respiration waveforms. Conclusions: WAVES is currently the largest pediatric-focused PW dataset available for open-access research and the second largest repository of correlated multi-channel PW data. The WAVES database can enable improvements in pediatric clinical care through machine learning research on PWs from a variety of hospitalized pediatric patients and could facilitate the development of methodological and clinical innovation in the field of pediatric care.
Abstract 14067: Outcomes of Transcatheter Aortic Valve Replacement Among Patients With Prior Coronary Artery Bypass Graft: A Nationwide Analysis
Authors: Abdelrhman Abumoawad, Hesham Mohamed Aly Afify, Hossam Alzu'bi, Mohammed Saleh, adel elmoghrabi, Hani Jneid, Wissam Khalife, Ayman Elbadawi
Journal: Circulation (2022)

Background: There is a paucity of data regarding the temporal trends and outcomes of transcatheter aortic valve replacement (TAVR) among patients with prior coronary artery bypass graft (CABG) surgery. Methods: We queried the Nationwide Readmissions Database (2016-2019) for hospitalized patients who underwent TAVR using ICD-10 codes. We evaluated the trends and outcomes of TAVR among patients with versus without a history of prior CABG. Multivariable regression analysis was used to adjust for patients’ and hospitals' characteristics when comparing the study groups. The primary outcome was in-hospital mortality. Results: The final analysis included 173,274 admissions who underwent TAVR of whom 31,271 (18.3%) had a history of prior CABG. During the study years, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR (22.0% in 2016 vs. 16.2%, Ptrend=0.01), while there was no change in their in-hospital mortality rate (1.08% in 2016 vs. 1.25% in 2019, Ptrend= 0.43). Patients with prior CABG were younger and less likely to be women compared with those without prior CABG. On multivariable adjustment, In-hospital mortality was lower among the group with versus without prior CABG (adjusted odds ratio [aOR] 0.77; 95% confidence interval [CI] 0.65-0.91, p&lt;0.01). Adjusted analysis showed lower rate of 90-day readmission (OR 0.95; 95%CI 0.90-0.98, p=0.01), and similar rate of ischemic stroke (aOR 0.89; 95%CI 0.76-1.03, p=0.89), permanent pacemaker (PPM) implantation (aOR 0.99; 95%CI 0.93-1.05, p=0.99). Among those with prior CABG, female gender, and chronic kidney disease ≥3 were independently associated with higher in-hospital mortality, and obesity was associated with lower in-hospital mortality. Conclusion: In this analysis, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR. TAVR among those with prior CABG was not associated with increased short-term mortality or PPM implantation.
Abstract 13520: Impaired Prenatal Brain Development Predicts Adverse Neurodevelopmental Outcomes in Infants With Congenital Heart Disease
Authors: Yao Wu, Nickie Andescavage, Kushal Kapse, Anushree Kapse, Yushuf Sharker, Catherine Lopez, Mary T Donofrio, Gilbert Vezina, David Wessel, Adré J du Plessis, Catherine Limperopoulos
Journal: Circulation (2022)

Introduction: Fetuses with complex congenital heart disease (CHD) are at high risk for impaired brain development. However, the relationship between altered fetal brain development and infant neurobehavioral outcomes in CHD remains largely unknown. Hypothesis: We hypothesized that impaired fetal brain volumetric growth and cortical folding in CHD would predict impaired infant neurodevelopment. Methods: We prospectively recruited women with pregnancies complicated by a fetal CHD diagnosis. Women underwent a fetal MRI on a GE 1.5T scanner. Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem were quantified. Cortical folding included local gyrification index, sulcal depth, and surface area. We completed Bayley Scales of Infant and Toddler Development III and Infant-Toddler Social and Emotional Assessment at 18 months. Generalized estimating equations were used to measure associations between fetal brain measures and infant neurodevelopment outcomes. Results: We enrolled 186 mother/baby dyads who underwent 250 MRIs between 20-39 gestational weeks. Seventy-seven had single-ventricle (SV) CHD and 109 had two-ventricle (2V) CHD. Forty-nine subjects died and 133 infants underwent neurodevelopment testing at a mean age of 19.6 months. Decreased fetal brain volumes and delayed cortical folding (all p&lt;0.05) were associated with poorer infant cognitive outcomes. Impairments in fetal cerebellum (p=0.004), cortical (p=0.05) and deep gray matter (p=0.03) volumes, and cortical folding measures (all p&lt;0.01) were associated with language delays. Reduced prenatal cortical gray matter volume (p=0.008), gyrification (p=0.02), and surface area (p=0.05) were associated with motor delays. Infants with SV CHD had lower competence scores compared to 2V CHD. Conclusions: We report that impairments in fetal brain growth and cortical folding predict adverse cognitive, language and motor outcomes in CHD. Infants with SV CHD showed greater susceptibility to social-emotional problems compared to those with 2V CHD. These data suggest that impaired prenatal regional brain growth disturbances and delayed cerebral cortical development are important biomarkers for later neurobehavioral dysfunction.